Conventional prothrombin time (PT) assays have limited sensitivity and dynamic range in monitoring the anticoagulant activity of direct factor Xa inhibitors. Hence, new assays are needed. We modified a PT assay by adding calcium chloride (CaCl2) to the thromboplastin reagent to increase assay dynamic range and improve sensitivity. Effects of calcium and sodium ion concentrations, and sample handling, were evaluated to optimize assay performance. Increasing concentrations of calcium ions produced progressive increases in PT across the factor Xa inhibitor concentrations of 0 to 2500 nmol/L for razaxaban and apixaban. The greatest effect was seen when the thromboplastin reagent was diluted 1:2.25 with 100 mmol/L CaCl2 (thus selected for routine use). The optimized assay showed an interassay precision of 1.5 to 9.3 percentage coefficient of variation (%CV) for razaxaban and 3.1 to 4.6 %CV for apixaban. We conclude that the modified PT assay is likely to be suitable as a pharmacodynamic marker for activity at therapeutic concentrations of factor Xa inhibitors.

01 Jan 2012·Journal of Thrombosis and ThrombolysisQ4 · MEDICINE

The impact of factor Xa inhibition on axial dependent arterial thrombus formation triggered by a tissue factor rich surface

Q4 · MEDICINE

Article

Author: Gavin E. Jarvis ; Nicholas Pugh ; Richard W. Farndale ; Bill Davis ; Kjell S. Sakariassen ; Annelize Koch

This study was designed to assess the effect of Factor Xa antagonists on thrombus formation at various axial positions on a tissue factor rich surface under arterial blood flow conditions. Non-anticoagulated, flowing human blood, drawn directly from an antecubital vein, was perfused over a tissue factor coated cover slip in a parallel-plate perfusion chamber. Thrombus surface coverage, thrombus mean height and fibrin surface coverage were measured at six different axial positions by confocal microscopy. Both thrombus surface coverage and mean height decreased along the cover slip axis whereas the fibrin surface coverage increased. Pre-chamber treatment of blood with the direct Factor Xa inhibitors Razaxaban and 813893 resulted in significantly reduced thrombus and fibrin formation at all axial positions investigated (P < 0.05). Thrombus and fibrin deposition in a laminar flow chamber changed with axial position with surface coverage measurements being more reproducible than thrombus mean height. Data were more reproducible towards the centre of the flow chamber than at the extremities. Razaxaban and 813893 inhibited thrombus and fibrin formation at the highest concentrations tested. No difference in drug effect was apparent at different axial positions. In conclusion, axial position influences the degree of thrombus and fibrin deposition with measurements being less reproducible at the extremities of the flow chamber. This technique may prove useful for analysing anti-thrombotic drug effects before progression to clinical trials.

01 Mar 2009·Vnitrni lekarstvi

[Advances in antithrombotic treatment--antithrombotics with anti-Xa effect].

Review

Author: Bátorová, A

The use of anticoagulants in the prophylaxis and treatment of arterial and venous thrombosis has substantially expanded during the last years. Increasing knowledge about the inherited and acquired thrombophilia and the risk factors predisposing to the recurrency of thromboembolic events result in a new indications for primary and secondary thromboprophylaxis with prolonged or even life-long duration. The limitations of classical anticoagulans, heparin and vitamin K antagonists support the development of medicaments with a specific antithrombotic action. The new generation anticoagulants inhibit in a specific way either particular coagulation enzyme or hemostasis activation step. Based on the in vitro studies and extensive clinical observations the activated factor Xa (FXa) seems to be one of the most advantageous targets for a specific action of perspective antithrombotic agents. Two selective F Xa inhibitors have been approved for clinical use: fondaparinux is an indirect parenteral F Xa inhibitor, and most recently approved rivaroxaban is the first oral anti-Xa inhibitor. Other anti-Xa molecules are under development for either parenteral (idraparinux, DX-9065a) or oral use (razaxaban, apixaban, rivaroxaban, LY-51, 7717, BMS-56247 a DU-176b).

100 Deals associated with Razaxaban Hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D04029	-	-	-

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Indication	Highest Phase	Country/Location	Organization	Date
Thrombosis	Phase 2	-	Bristol Myers Squibb Co.	-
Thrombosis	Phase 2	US	-	-

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